Wojciech Stec (Polish Academy of Sciences, Łódź)

A team of Polish inventors discovered a method that enables the production
of DNA and RNA components and their analogs in a simple and cost-efficient
manner.

Led by Wojciech Stec at the Polish Academy of Sciences’ Centre of
Molecular and Macromolecular Studies in Lodz, a group of Polish scientists
filed a patent application in 1992 on their breakthrough in the methods
and compounds for synthesising P-chiral oligonucleotide analogs.

In their patent (published in 1998) the scientists claimed they had discovered
a method enabling the production of DNA and RNA components and their analogs.
But the real innovation was that they were making the compounds available
in a pre-defined, spatial alignment. These special compounds, they hoped,
might be used as customised medication or as tools in diagnostics, forensic
medicine and criminalistics.

His work has taken the award-winning inventor Stec around the world, and
he has worked as a visiting professor in several countries while enjoying
great respect for his discoveries from fellow experts.

In assessing the invention, Dr John Love, an independent expert at Exeter
University’s school of biological sciences, explains that oligonucleotides
are a workhorse of molecular biology and are used in many applications,
“the most significant probably being PCR (the polymerase chain reaction)
which is the basis of certain types of gene cloning, DNA sequencing and
DNA fingerprinting.”

The patent also claimed that the availability of synthetic oligonucleotides
and a variety of nuclease-resistant analogs such as phosphorothioates
and methylphosphonates has encouraged investigation into their use as
therapeutic compounds for treating a variety of conditions associated
with the inappropriate expression of indigenous and exogenous genes.
John Rossi, another independent expert on the matter, is chairman professor
of molecular biology at the Beckman Research Institute in California,
one of America’s major centres for pioneering biomedical research.
He feels the breakthrough by Stec and his team is significant “to
the extent that chiral containing phosphate or phosphorothioate linkages
are being used in antisense molecules.”

Rossi continued: “The phosphorothioates are very chiral, and were
popular a few years ago because of various stability and hybridisation
properties. They lost favour because of toxicity, perhaps in part due
to chirality. It remains to be seen in non-chiral PS oligonucleotides
will regain favour.”

Rossi said the patent’s significance depends on the biological efficacy
of such non-chiral backbones and notes that it “may be a useful
patent for specific modifications of the ends of the molecules if it stabilises
them in sera without affecting activity.”

The patent for Poland – granted before the European one –
was licensed to Applied Biosystems Inc, then Lynx Therapeutics Inc and
finally Inex Inc. Its commercial development was killed off, however,
when the Federal Drug Administration in the United States approved the
AIDS drug Vitravene in 1998. The decision effectively ended other antisense-drug
companies’ interest in the patent.

The rights to the invention returned to the Centre of Molecular and Macromolecular
Studies, but in 2002 they were purchased by Genta Inc, a New Jersey-based
biopharmaceutical company that develops drugs to treat cancer patients.

Patent co-author Stec received the Foundation for Polish Science award
(known as the Polish equivalent to the Nobel Prize) in 2004. He has been
a visiting professor to medical institutes in Germany, China, Japan and
the United States, and is still connected to the Centre of Molecular and
Macromolecular Studies as the head of its bioorganic chemistry division.

Stec continues his work in many fields, including the medicinal applications
of oligonucleotides, the area this unique invention also focused on.